paracelcus reloaded: searching for the perfect dose of exercise? · 2015. 7. 2. · paracelcus...
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Paracelcus Reloaded: Searching for the Perfect Dose of Exercise?
Professor Sanjay Sharma St George’s University of London
St George’s Hospital NHS Trust [email protected]
@SSharmacardio
Conflicts/Disclosures: None
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• To provide a brief overview of the recognised benefits of physical activity on cardiovascular health.
• To discuss the currently recommended dose of physical activity for all individuals.
• To question whether too much exercise may have a deleterious impact on an otherwise normal heart.
Objectives
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Physical activity and CVD: Early Work
The first study to show an association between physical activity and risk of heart disease.
Morris et al. (1953) Lancet
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Risk Hazard of CHD in Relation to Physical Activity
N = 44,452 professional males Follow up of 475,755 person years
Tenesescue M et al JAMA 2002
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Death Rates as a Function of Cardiovascular Fitness
Church TS. Arch Int Med 2005 Kokkinos P et al Circulation 2008
9km/h
6.4 km/h
13% reduction per MET
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15 year observational study. 55,137 individuals. Mean age 44 years old. Runners had a 30% all cause reduction in mortality and a 45% reduction in CVD events.
Duck Chul-Li et al. JACC 2014
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Schnohr et al. JACC 2015
1098 joggers and 3,950 healthy non joggers. Jogging 1-2.4 hours, over 2-3 times per week and a slow to moderate pace (6-10 MET equivalents) was associated with the best results for reduction in all cause mortality.
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Current Physical Activity Guidelines
• Adults:
30 mins of moderate intensity physical activity at least days per week
or 25 min vigorous activity 3 days per week
• Children: at least 60 minutes per day of moderate intensity physical activity.
(Chief Medical Officers Report 2004)
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Endurance Athletes
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Risks and harms
Cardiovascular Benefit
Bene
fits
of
exerc
ise
Exercise intensity
Dose-Benefit Relationship
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The Young Athlete’s Heart
10% increase in LV and RV cavity. 10-20% increase in left ventricular wall thickness
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Left Ventricular Cavity Dimensions in Highly Trained Athletes
48%
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44 Italian Olympian males with LVH (> 13 mm) and enlarged LV cavity (> 60 mm). De-trained for a mean of 53 months. LV wall thickness and LV mass normalised.
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The Ugly Side of Exercise: Sudden Cardiac Death
90% during or just after exercise 90% in males 80% don’t have prodromal symptoms 40% in age < 18 years old
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Dehydration Adrenergic surges
Electrolyte imbalance
Acid/base disturbance
Triggers for Sudden Cardiac Death
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Can Exercise Induce Cardiomyopathy in a Normal Heart?
Endurance athletes
exercise 10-15 x the daily
recommended exercise.
2 million marathon
participants each year.
Can you get too much of a
good thing?
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Evidence of Transient Cardiac Injury Post Marathon Running
• Raised cardiac troponin levels post race (EXERCISE INDUCED CARDIAC DAMAGE)
• Impaired left ventricular function
(EXERCISE INDUCED CARDIAC FATIGUE)
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Troponin
Troponin
Troponin
Could Too Much Exercise Be Cardiotoxic?
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Troponin Release
High BNP concentrations
Myocardial inflammation
Myocardial fibrosis
Adverse cardiac remodelling
Cardiac Dysfunction
+
Arrhythmias
PATHOLOGY HISTOLOGICAL CHANGES
SEROLOGICAL MARKERS
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Animal model of Endurance Training
Exercised for 60mins daily
for 16 weeks
Compared with sedentary rats
E
A
Diastolic dysfunction
VT in 42 %
Enlarged Atria and RVH/LVH
Fibrosis
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102 healthy males aged 50-72 years old. Completed at least 5 marathons in the past 3 years. 12 had late gadolinuim enhancement which was 3-fold commoner than in age-matched controls. 5 had LGE with a coronary artery disease pattern. 7 had non specific patchy fibrosis.
Breuckmann. Radiology 2009
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Atrial Fibrillation in Athletes
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Atrial Fibrillation in Sportsmen
Incidence 5-10% of middle aged endurance athletes Risk of lone AF over 5-fold greater than in matched sedentary individuals. Usually sportsmen who have been exercising since youth.
Almost all male.
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Risk factors for Atrial Fibrillation in Athletes
Lone Atrial Fibrillation in
Athletes Male sex
Age 40-60
Endurance sport
Tall stature
Exercise time 1500 hours over
a life time
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AF in Athletes Trigger
?Increased pulmonary vein ectopy
Endurance sport
practice Modulators
Increased vagal tone: Bradycardia Shortening and dispersion of the atrial refractory period Gastro-oesophageal reflux
Substrate
Pressure and volume overload: Atrial stretch Myocyte Hypertrophy
Atrial dilatation Inflammatory response Atrial fibrosis
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Former professional cyclists Golfers (n=62) (n=62) ______________________________________________________ Mean age 66 ± 6 yrs 66 ± 7 yrs QRS 102 ± 20 msec 99 ± 13 msec HR 66 ± 9 bpm 70 ± 8 bpm SND 10% 2% Pacemaker 3% 0% Pauses > 2.5 s 6% 0% Atrial flutter 6% 0% NSVT 15% 3%
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Former professional cyclists Golfers (n=62) (n=62) ______________________________________________________ Mean age 66 ± 6 yrs 66 ± 7 yrs QRS 102 ± 20 msec 99 ± 13 msec HR 66 ± 9 bpm 70 ± 8 bpm SND 10% 2% Pacemaker 3% 0% Pauses > 2.5 s 6% 0% Atrial flutter 6% 0% NSVT 15% 3%
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Studied participants in the Vasalopett (90k) cross country ski race between 1989-1998. 90% Male. Followed by until December 2005. 959 had significant arrhythmias (AF, A flutter and bradyarrhythmias) which correlated with the number of races completed and faster finishing times; HR 1.30 each.
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46 endurance athletes
Symptoms n = 36 Syncope 65% Aborted SCD 2% Palpitation 15%
Complex ventricular arrhythmias
Very abnormal ECG in 58% VT or RV origin in 49% Criteria for ARVC in 59%
9 died suddenly and 9 got ICD
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22 symptomatic athletes; cyclists (77%)
Arrhythmias of right ventricular origin
Right ventriculography revealed enlarged right ventricles with reduce ejection fraction
Possible explanations:
1. Increased RV work load may unmask heterozygotes for ARVC
2. Exercise causes adverse remodelling of the RV and increases risk of arrhythmias
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n = 47
51% ‘Definite ARVC’ by TFC
36% ‘Suspected ARVC’ by TFC
An ARVC-like phenotype may be acquired through
intense exercise
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40 healthy endurance athletes Assessed immediately before, after and 7 days after an ultra-endurance race. Troponin levels correlated with magnitude of RV dysfunction
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Right Ventricular Exercise Physiology REST Left Ventricle Right
Cardiac output (l/min) 5 5 Vascular resistance (dyne/sec/cm3) 1100 70 Load pressure (mm Hg) 130/75 (85) 25/9(15)
EXERCISE
Cardiac output (l/min) 25 25 Vascular resistance (dyne/sec/cm3)
Load pressure (mm Hg)
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108 Males aged 50-72 years old High calcium scores and late gadolinium enhancement in presumably healthy middle aged marathon runners compared with Framingham risk matched controls Marathon running associated with a 2-fold increase in LGE.
56% runners were current or former smokers
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Myocyte necrosis
(cTn rise)
Cardiac arrhythmias
Dilated Cardiomyopathy
Chronic endurance exercise
? Myocardial scars
RV Pressure
Arrhythmogenic right ventricular cardiomyopathy
Adverse atrial remodelling
Atrial fibrillation High degree AV block
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114 athletes (78% Male) Mean age 22 ± 4 Continuous intensive physical training for at least 2 consecutive Olympics (2-5) Mean training period 8.6 ± 3 years (4-17) Rowers and canoeists (n=55), cyclists (n=19), cross-country skiing (n =15) long distance running/marathon (n=9), swimming (n=6) triathlon (n=2)
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Aging is associated with decreased left ventricular compliance and distensibility. 4-5 sessions of intensive exercise for 30 minutes per week over 25 years prevented such age related changes. Lower doses of exercise did not retard this normal aging process. Masters athletes exhibited the most compliant ventricles. and may reduce the risk of hypertension and heart failure with preserved ejection fraction
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Schnohr et al. JACC 2015
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BJSM 2011
Elite Endurance Athletes Live Longer than Non Athletes
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Sudden Cardiac death
in sport
Acute Myocardial infarction
Alcohol
Diabetes
Obesity
Prostate cancer
Smoking related deaths
0 50 100 150 200 250
32
12.8
58.8
Mortality rate per 100,000 population
68.6
23.9
207
2
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Died age
51
May he
rest in
peace
Marathon Runners
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Numerator versus Denominator
Athletes with
disease phenotypes
(based on case reports
and small cohort studies)
Athletes with raised markers of cardiac
damage
Apparently Healthy Ultra-endurance runners
(millions)
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CARDIOTOXIC
?
Prospective Studies
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Conclusions
Moderate exercise has cardiovascular benefits. Long term endurance exercise promotes atrial fibrillation in some athletes. Larger prospective studies are necessary to confirm or refute whether life long endurance exercise exerts a plethora of deleterious effects on an otherwise normal heart.